Cancer represents a significant burden on human health, accounting for an estimated 13% of all deaths each year. In particular, several common cancers and diseases are associated with androgen hormone signaling, such as, for example, prostate cancer, breast cancer, ovarian cancer, bladder cancer, pancreatic cancer, and polycystic ovary disease. For example, prostate cancer (PCa) is the second most common cancer in men. The majority of prostate cancer deaths are due to the development of metastatic disease that is unresponsive to conventional androgen deprivation therapy. Androgen deprivation therapy has been the standard of care in subjects with prostate cancer since the 1940s. Despite androgen deprivation, most subjects ultimately experience disease progression. For many years this later phase of the disease was called “hormone insensitive prostate cancer” or “androgen independent prostate cancer.” It has since become clear that the prostate cancer that emerges after androgen deprivation therapy remains dependent upon androgen. The prostate cancer cells that have survived have gained the ability to import low levels of circulating androgens (expressed from adrenal glands), become much more sensitive to these low levels of testosterone, and actually synthesize testosterone within the prostate cancer cell itself. This stage of prostate cancer is now termed “castration resistant prostate cancer” or CRPC.
Identification of patients that are likely to respond or identification of those patients that are responding to therapy for prostate cancer is a goal for medical management of this disease. While current clinical guidelines are focused on symptoms, blood levels of prostate specific antigen (PSA), and imaging studies, other biological markers may be useful for clinical decision making. There remains a need for biomarkers of the disease and their relationship to identification of efficacy or toxicity of a therapeutic compound, and biomarkers which could provide information regarding identification of patients most likely to respond to therapeutic agents, or to identify patients receiving therapeutic agents who are not responding (either through primary or acquired resistance mechanisms), or to predict those patients that may develop undesirable side effects.